Alcohol continues to be the number one substance of abuse among adolescents. Adolescence represents a critical window of vulnerability for initiating alcohol use, and in a large number of cases leading to increased alcohol intake. It is well documented that adolescents differ from adults in their sensitivity to alcohol. Our laboratory has reported that adolescent male rats, but not adult male rats, exposed to alcohol exhibit significant deficits in spatial learning and memory. The performance deficits persist for a significantly long period of time after the alcohol exposure is over. Alcohol in female adolescent rats also causes profound deficits in spatial learning and memory, but unlike adolescent male rats, their deficits do not persist beyond the alcohol exposure period. We have further shown that adolescent alcohol-induced behavioral deficits are associated with alterations in N-methyl-D-aspartate (NMDA) receptors in the brain. This proposal will explore the nature, mechanisms and consequences of alcohol exposure during adolescence on learning and memory in male and female rats, and the influence of pubertal gonadal hormones on alcohol behavior. We will test the overarching hypothesis that during adolescence pubertal gonadal hormones influence alcohol-induced behavioral deficit by modulating the NMDA receptor. The proposed rodent studies will (1) confirm and characterize the pharmacology of alcohol-induced memory deficit in adolescent rats, (2) examine the role of pubertal gonadal hormones in adolescent alcohol-induced memory deficit, (3) study modulation of NMDA receptor by pubertal gonadal hormones following adolescent alcohol exposure, (4) investigate signaling molecules that are affected by adolescent alcohol, (5) determine structural changes in the brains of adolescent alcohol exposed rats. These studies will employ a multidisciplinary approach comprising of biochemical, molecular, behavioral and anatomical techniques. Understanding age-related changes in the brain as it transitions from adolescence to adulthood, and the effects of pubertal gonadal hormones on alcohol-induced behavioral deficits will provide clues as to why the adolescent period is particularly vulnerable to use and abuse of alcohol, and lead to novel therapeutic targets that may be used for prevention and/or treatment of adolescent alcohol use and abuse. [unreadable] [unreadable] [unreadable]